The primary objective of this program is the preparation and initial biological evaluation of analogs of the antitumor antibiotic adriamycin with a view toward improving the therapeutic efficacy, extending the antitumor spectrum, and/or reducing the toxicity of the parent anthracycline. Based upon earlier findings in these laboratories of the therapeutic superiority and lesser toxicity of N-trifluoroacetyladriamycin-14-valerate (AD 32), compared to adriamycin in animal systems, various adriamycin analogs have been prepared as candidate anticancer agents and to explore the structure-activity relationships among natural and synthetic anthracyclines. Analogs already prepared or currently under development include a variety of 14-position modifications (acyloxy, ether, aza, and thia), 13-dihydro derivatives, and anthracyclines with fraudulent (non-daunosamine) glycosides. Agents are evaluated in appropriate in vitro and in vivo bioassay systems for cytotoxicity and antitumor activity.